Difficulty: Intermediate | Prerequisites: SN1/SN2 basics (Ch. 7), alcohol functional group chemistry
This material sits at the intersection of nucleophilic substitution and functional group transformations. You need a solid handle on how leaving groups work and why alcohols are poor substrates for direct substitution. If SN2 mechanism basics feel shaky, revisit Chapter 7 before diving in. The oxidation side connects forward to carbonyl chemistry, which dominates the second half of the course.
Alcohols have a poor leaving group (OH−), so you convert the –OH to a tosylate (–OTs) first, then run an SN2 with a nucleophile like iodide. The SN2 step inverts stereochemistry at the carbon bearing the leaving group. Separately, you can oxidise alcohols to aldehydes, ketones, or carboxylic acids depending on which reagent you choose (PCC stops at the aldehyde; Jones or chromic acid pushes primary alcohols all the way to the carboxylic acid).
Tosylate (OTs)
The sulfonate ester formed when an alcohol reacts with p-toluenesulfonyl chloride (TsCl). It converts the –OH into an excellent leaving group.
In simple terms, tosylation swaps out a stubborn –OH for a group that actually wants to leave.
Pyridine
A weak, non-nucleophilic base used during tosylation to mop up the HCl produced.
Think of it as the cleanup crew: it keeps the reaction mixture from becoming acidic.
SN2 (bimolecular nucleophilic substitution)
A one-step mechanism in which a nucleophile attacks the electrophilic carbon at the same time the leaving group departs. The rate depends on both the substrate and the nucleophile concentration.
In simple terms, the nucleophile shoves the leaving group out the back door, which flips the stereochemistry.
Inversion of configuration (Walden inversion)
The stereochemical outcome of every SN2 reaction: the product has the opposite R/S designation at the carbon where substitution occurred.
Think of an umbrella flipping inside out in the wind.
PCC (pyridinium chlorochromate)
A mild chromium-based oxidant that converts primary alcohols to aldehydes and secondary alcohols to ketones. It does not over-oxidise to carboxylic acids.
In simple terms, PCC is the gentle oxidiser: it stops at the aldehyde stage.
Jones reagent (CrO3 / H2SO4 / acetone)
A strong oxidant that converts primary alcohols all the way to carboxylic acids and secondary alcohols to ketones.
Think of Jones as the heavy-duty option: primary alcohols go straight through the aldehyde and end up as acids.
DMSO (dimethyl sulfoxide)
A polar aprotic solvent commonly used in SN2 reactions. It dissolves ionic nucleophiles well and does not solvate anions strongly, leaving them free and reactive.
In simple terms, DMSO keeps the nucleophile "naked" and ready to attack.
Hydroxide (–OH) is a terrible leaving group. You cannot simply add NaI to an alcohol and expect substitution.
Treating the alcohol with TsCl in pyridine converts –OH to –OTs, which is an excellent leaving group (the conjugate base of a strong acid, p-toluenesulfonic acid, pKa ≈ −1).
Tosylation does not break any bonds at the stereogenic carbon, so the configuration at that carbon is retained.
Once the tosylate is in place, a strong nucleophile (here, NaI in DMSO) attacks the electrophilic carbon from the back side.
This back-side attack forces inversion of configuration at that carbon.
DMSO is chosen because it is polar aprotic: it dissolves NaI but does not cage the iodide anion, keeping it highly nucleophilic.
Starting material: a cyclopentene with –OH at C-3. After tosylation (retention) and SN2 with NaI (inversion), the product is 3-iodocyclopentene with inverted configuration at C-3.
If the starting alcohol is (S), the tosylate is still (S), and the iodide product is (R). The answer to Q1 is (b) (R)-3-iodocyclopentene.
Step 1, tosylation:
The oxygen lone pair of the alcohol attacks the sulfur of TsCl.
Chloride departs.
Pyridine deprotonates the oxonium ion to give the tosylate ester.
Step 2, SN2:
Iodide attacks the carbon bearing the OTs from the back side (180° to the C–OTs bond).
The C–OTs bond breaks simultaneously.
One curved arrow from I− to C, one curved arrow from the C–OTs bond to OTs−.
Starting material | Product | Reagent(s) |
|---|---|---|
Primary alcohol (RCH2OH) | Aldehyde (RCHO) | PCC (in CH2Cl2) |
Primary alcohol (RCH2OH) | Carboxylic acid (RCOOH) | Jones reagent (CrO3/H2SO4), KMnO4, or H2CrO4 |
Secondary alcohol (R2CHOH) | Ketone (R2C=O) | PCC, Jones, or any Cr(VI) reagent |
Tertiary alcohol (R3COH) | No reaction | Tertiary alcohols cannot be oxidised (no C–H on the carbinol carbon) |
If you need to stop at the aldehyde, use PCC. It works in anhydrous CH2Cl2, so there is no water around to hydrate the aldehyde and push it further.
If you want the carboxylic acid from a primary alcohol, use Jones reagent or another strong oxidant. The aqueous acidic conditions hydrate the intermediate aldehyde, enabling a second oxidation.
For secondary alcohols, any of the chromium reagents give the ketone. There is no risk of over-oxidation because the ketone has no C–H on the carbonyl carbon to lose.
The recitation asks you to identify functional groups in the starting materials and products of each oxidation. Keep these straight:
–COOH = carboxylic acid
–CHO = aldehyde
C=O (flanked by two carbons) = ketone
–OH on sp3 carbon = alcohol
Alcohol oxidation is how breathalysers work: ethanol in your breath is oxidised by a Cr(VI) reagent, producing a colour change from orange to green. The degree of colour change correlates with blood alcohol concentration.
Students often think tosylation inverts stereochemistry. It does not. Tosylation only changes what is bonded to the oxygen; no bonds to the stereogenic carbon are broken, so configuration is retained.
Students sometimes assume any strong oxidant can stop at the aldehyde stage. PCC stops at the aldehyde specifically because it operates in anhydrous conditions. Jones reagent, which uses aqueous acid, pushes all the way to the carboxylic acid.
A common error is writing SN1 for a primary or secondary tosylate in a polar aprotic solvent with a strong nucleophile. When the nucleophile is strong and the solvent is polar aprotic, the mechanism is SN2 regardless.
Students forget that tertiary alcohols cannot be oxidised. If a question shows a tertiary alcohol with an oxidising agent, the correct answer is "no reaction."
⚠️ Tosylation + SN2 is a two-step workaround that appears constantly on exams. If you see an alcohol being converted to a halide with retention of the carbon skeleton but inversion of stereochemistry, this is the pathway.
⚠️ Know the difference between PCC and Jones reagent cold. Exam questions frequently give you a primary alcohol and ask for the product under each set of conditions.
⚠️ Arrow-pushing for the SN2 step requires exactly two arrows: one from the nucleophile to the electrophilic carbon, one from the C–LG bond to the leaving group. Getting this wrong loses marks even if you identify the correct product.
⚠️ Questions that combine tosylation with stereochemistry (as in Q1) test two things at once: whether you know tosylation retains configuration and whether you know SN2 inverts it. The net result of the two-step sequence is inversion.
True or false: Tosylation of an (R)-alcohol gives an (S)-tosylate. (False. Tosylation retains configuration.)
Fill in the blank: PCC oxidises a primary alcohol to a(n) ______. (Aldehyde.)
True or false: SN2 reactions proceed with retention of stereochemistry. (False. SN2 always inverts.)
Fill in the blank: Jones reagent oxidises a primary alcohol to a(n) ______. (Carboxylic acid.)
True or false: DMSO is a polar protic solvent. (False. DMSO is polar aprotic.)
Q: An (S)-secondary alcohol is treated with TsCl/pyridine, then NaI in DMSO. What is the stereochemistry of the product?
A: (R). Tosylation retains configuration; SN2 with iodide inverts it. Net result is inversion of the original alcohol's configuration.
Q: You need to convert 1-butanol to butanal. Which reagent do you use, and why?
A: PCC in CH2Cl2. PCC is a mild, anhydrous oxidant that stops at the aldehyde. Jones reagent would push the oxidation all the way to butanoic acid.
Q: A secondary alcohol is treated with Jones reagent. What is the product?
A: A ketone. Secondary alcohols give ketones with any chromium(VI) oxidant, and there is no risk of further oxidation.
Q: Why is pyridine used in the tosylation step rather than, say, NaOH?
A: Pyridine is a non-nucleophilic base. It neutralises the HCl by-product without competing as a nucleophile. NaOH is both a base and a nucleophile, which could interfere.
Q: Draw the arrow-pushing mechanism for the SN2 reaction of a tosylate with iodide.
A: One arrow from I− lone pair to the electrophilic carbon (back side). One arrow from the C–OTs bond to OTs. Two arrows total, one concerted step.
Tosylation links directly to the Williamson ether synthesis (covered in the next set of notes): an alkoxide attacks a tosylate or alkyl halide via SN2, so all the same stereochemical and steric rules apply. Alcohol oxidation connects forward to carbonyl chemistry (aldehydes, ketones, carboxylic acids), which forms the backbone of the second semester of organic chemistry.
Related Terms / Search Tags
Tosylate, TsCl, p-toluenesulfonyl chloride, tosylation, OTs, leaving group conversion, SN2 mechanism, Walden inversion, back-side attack, nucleophilic substitution, NaI, DMSO, polar aprotic solvent, PCC, pyridinium chlorochromate, Jones reagent, CrO3, chromic acid, alcohol oxidation, primary alcohol to aldehyde, primary alcohol to carboxylic acid, secondary alcohol to ketone, Cr(VI) oxidation, CHM 255, organic chemistry, Purdue